From Days to Hours: How Sequencing by Expansion (SBX) Is Redefining Genomic Discovery

Whole-genome sequencing has long been constrained by speed, cost, and access. SBX is designed to change all three.

Genomic sequencing has transformed our understanding of cancer, rare disease, and inherited conditions. But one fundamental constraint hasn’t changed: time. Days or weeks separate a sample from a result — and in research settings, delayed data means delayed discovery.

Sequencing by Expansion (SBX) is a novel, high-throughput single-molecule sequencing technology, currently for Research Use Only (RUO). It compresses sample-to-result timelines, scales high-accuracy whole-genome sequencing, and addresses operational barriers that have limited how far and how fast genomic research can go. 

The challenge: labs are being asked to do more with less

Genomic laboratories are under pressure from every direction: more samples, tighter budgets, less time. The dominant sequencing technology — sequencing by synthesis (SBS) — was built for a different era. Its cycle-based approach means data arrives slowly, serial workflows extend sample-to-result times to multiple days, and single-use consumables push per-sample costs higher if flow cells are run below maximum capacity, creating a cost penalty for sub-optimal batch sizes. Batch-size constraints make urgent or low-volume work inefficient, and data analysis piles up as a downstream bottleneck that demands heavy computing infrastructure and specialist support.

Nanopore sequencing emerged as an alternative, but faces a fundamental limitation: when DNA passes through the pore, the signal is noisy and difficult to read with precision. Traditional methods often require expensive instrumentation, suffer from slow turnaround times, or penalise laboratories that want to run small, urgent batches.

 This means that high-quality sequencing at scale has been kept out of reach by cost and complexity for many laboratories. The overarching challenge has been finding a way to deliver sequencing that is efficient, fast, and cost-effective enough for broader, routine adoption — and build the large-scale genomic evidence base that health systems urgently need.

SBX solves the signal problem before sequencing even begins

SBX takes a different approach entirely. Rather than reading DNA directly, it first converts the DNA sequence into a purpose-built surrogate molecule called an Xpandomer. This Xpandomer is more than 50 times longer than the original DNA strand, which creates wide, clear spacing between the signal markers that identify each base — solving the noise problem at source¹.

Sequencing is then performed on a re-usable sensor chip containing around eight million individual pores². Both strands of the original DNA are read and cross-checked, yielding accuracy scores above 99.80% for single-letter variants². Because base calling begins in real time as each Xpandomer translocates, and analysis runs concurrently on a local accelerated pipeline, the gap between sample and result compresses dramatically. 

The outcome: same-day whole-genome sequencing 

In October 2025, researchers from Broad Clinical Labs, Roche Sequencing Solutions, and Boston Children’s Hospital published a landmark study in the New England Journal of Medicine — and set a Guinness World Record in the process³.

Using an optimised SBX workflow, the team sequenced 15 human samples end to end — from sample processing through sequencing, analysis, quality control, and variant prioritisation a— in under four hours³. This surpassed the previous record by more than an hour. Crucially, samples included cases from Boston Children’s neonatal intensive care unit, where the findings demonstrated that a same-day, blood-to-report workflow of under eight hours is within reach in a research context⁴.

“For some families, this genetic result is the keystone to their entire care plan, and waiting even for two days is an eternity,” said Monica Wojcik, MD MPH, Attending Physician at Boston Children’s Hospital and first author on the study. 

The study was conducted for research purposes only. No clinical diagnosis was performed.

“Together with Roche Sequencing Solutions and Boston Children’s Hospital, we demonstrated that rapid sequencing and interpretation are achievable in a matter of hours,” said Niall Lennon, PhD, Chief Scientific Officer of Broad Clinical Labs. “That brings us one step closer to a future where genetic answers can inform urgent decisions at the bedside.”

Note: The Broad Clinical Labs study was conducted for research purposes only. No clinical diagnosis was performed.

SBX is faster & more flexible — without compromising on accuracy

The same technology behind the four-hour turnaround makes that speed achievable across very different research workflows. And for molecular lab leads, SBX also lifts two of the biggest operational constraints: re-usable sensor arrays strip out the cost of single-use consumables, and the on-premise analysis pipeline removes the dependency on external computing infrastructure.

SBX also supports multiple sequencing modes on a single platform: high-accuracy duplex whole-genome sequencing for large cohorts, a streamlined configuration for urgent research samples with a design goal of sample to variant call in under five hours, and a simplex mode for high-throughput transcriptome applications. Open pipeline interfaces mean it can integrate with existing laboratory informatics environments and third-party analysis tools without a wholesale infrastructure change.

For research teams, the gap between sequencing and analysis shrinks: data can be interpreted while a run is still under way, rather than only after it finishes.

Implications beyond the lab: scaling genomics across health systems

Access to high-quality genomic data at population scale is a prerequisite for evidence-based precision medicine — and it doesn’t yet exist in most health systems. Per-sample costs, long turnaround times, and the concentration of sequencing capacity in a small number of specialist centres have kept genomic datasets fragmented, limited in diversity, and difficult to sustain across sites.

SBX potentially shifts the cost–time–throughput relationship in a way that makes large, diverse cohorts more tractable. Multi-centre studies and longitudinal monitoring programmes become easier to design and sustain, providing the essential evidence needed to evaluate patient outcomes. 

Crucially, this democratisation of sequencing infrastructure and costs grants access to regional and lower-resourced settings. By providing this scalable, high-fidelity data generation, SBX delivers the population-level genomic evidence health systems require to improve patient stratification, justify precision medicine investments, and allocate resources effectively.

What SBX means for oncology and rare disease research

Cancer is driven by specific genetic changes, and finding them fast — with precision — is what allows researchers to understand tumour biology and align treatment decisions with each patient’s disease. The challenge is that some of the most important mutations occur in regions of the genome that conventional short-read platforms handle poorly: structurally complex regions, repetitive sequences, areas of extreme GC content.

These are parts of the genome unusually rich or poor in the guanine and cytosine bases. Because GC content affects how stably DNA holds together and how evenly it can be sequenced, these regions are often under-represented in the resulting data, so the variants they contain are easily missed.⁵

SBX is designed to interrogate these regions reliably. Its high-accuracy duplex sequencing maintains variant-calling performance across single-letter changes, small insertions and deletions, copy number alterations, and structural rearrangements — with throughput of seven human genomes per hour at greater than 30× coverage.² 

For early detection research, it supports high-coverage whole-genome sequencing from low-input samples including circulating cell-free DNA. For longitudinal monitoring — tracking how cancer cells evolve, how resistance emerges, and whether residual disease persists after treatment — the combination of speed, accuracy, and scalability creates new research possibilities at the pace of clinical care.

For rare disease and paediatric genetics, the Broad/Boston Children’s study demonstrated that same-day whole-genome sequencing and analysis is achievable in a research workflow — a finding with direct implications wherever hours, not days, define the decision window.

Better outcomes begin with better data at scale

Detecting disease earlier and understanding it more precisely are the foundations of better outcomes — for patients, for families, and for health systems working to prevent, stop, and cure the conditions that carry the greatest burden. SBX is designed to help build the evidence base that makes this possible: faster, at greater scale, across more diverse populations, and in more settings than current sequencing infrastructure allows.

The SBX technology is for Research Use Only. The content of this article reflects current study results or design goals. Not for use in diagnostic procedures.